ROLE OF C-KIT IN EARLY HEMATOPOISESIS

C-KIT 在早期造血中的作用

• 批准号: 3087834
• 负责人: Carlos M. De Castro
• 金额: $ 7.02万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087834
• 关键词: anemia; bone marrow exam; cytokine; dyserythropoietic anemia; erythroleukemia; flow cytometry; gene expression; genetic promoter element; growth factor receptors; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; human fetus tissue; human subject; human tissue; immunoprecipitation; leukemia; luciferin monooxygenase; monoclonal antibody; polymerase chain reaction; protein tyrosine kinase; protooncogene; radioimmunoassay; receptor expression; reporter genes; tissue /cell culture; western blottings

Hematopoiesis is the process by which hematopoietic precursor cells undergo self-renewal and differentiation into the various mature blood cell lineages. Growth factor-receptor interactions play a significant role in the regulation of normal hematopoiesis, affecting both proliferation and differentiation of various hematopoietic lineages. Alterations of these receptors plays an important role in myelodysplasia and leukemogenesis. The kit proto-oncogene encodes for a tyrosine-kinase transmembrane receptor that is expressed on very early hematopoietic precursor cells, and is involved in stem cell migration and differentiation. The growth factor ligand for the kit receptor, known as stem cell factor, has been recently purified. The purpose of our study is to investigate the role of growth factor-receptor interactions on the regulations of hematopoiesis. We will investigate the role of the kit receptor in hematopoiesis by studying its expression and tyrosine kinase activity in both cultured cell lines and in hematopoietic cells isolated from bone marrow samples from human subjects. Expression of the kit receptor will be easily monitored using a monoclonal antibody which we have developed. The effects of various cytokines, including stem cell factor, on cells that express the kit receptor will be studied. Finally we will look for abnormal kit expression and/or function in patients with hematological disorders including leukemias, myelodysplastic disorders, and congenital anemias. Those patients whose cells show abnormal kit expression or function will be further investigated to define the defect at the molecular level. These studies should enhance our knowledge of the role of growth factor-receptor interactions in normal and abnormal states o hematopoiesis, thus leading to a better understanding of the pathophysiology of certain hematological diseases, and possibly lead to better therapies for these diseases.

造血是造血前体细胞经历的过程 自我更新和分化成各种成熟的血细胞 血统 生长因子-受体相互作用在 正常造血的调节，影响增殖和 各种造血谱系的分化。 修改这些 受体在骨髓增生异常和白血病发生中起重要作用。 kit原癌基因编码酪氨酸激酶跨膜受体 它在非常早期的造血前体细胞上表达，并且 参与干细胞迁移和分化。 所述生长因子 kit受体的配体，称为干细胞因子，最近已被 提纯 我们研究的目的是调查增长的作用 因子-受体相互作用对造血调控的影响。 我们将 研究kit受体在造血中的作用， 表达和酪氨酸激酶活性， 从人类受试者的骨髓样本中分离的造血细胞。 试剂盒受体的表达将使用单克隆抗体容易地监测。 我们开发的抗体。 各种细胞因子的作用， 包括干细胞因子，对表达kit受体的细胞的作用， 研究了 最后，我们将寻找异常试剂盒表达和/或功能 在患有包括白血病的血液疾病的患者中， 骨髓增生异常疾病和先天性贫血。 的那些患者 将进一步研究显示异常kit表达或功能的细胞 在分子水平上定义缺陷。 这些研究应加强 我们对生长因子-受体相互作用在正常发育过程中的作用的认识， 和异常状态的造血，从而导致更好地了解 某些血液病的病理生理学，并可能导致 更好的治疗方法